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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Gene-based pleiotropy across migraine with aura and migraine without aura patient groups</title><author><name sortKey="Zhao, Huiying" sort="Zhao, Huiying" uniqKey="Zhao H" first="Huiying" last="Zhao">Huiying Zhao</name><affiliation><nlm:aff id="A1">Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A2">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Eising, Else" sort="Eising, Else" uniqKey="Eising E" first="Else" last="Eising">Else Eising</name><affiliation><nlm:aff id="A3">Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="De Vries, Boukje" sort="De Vries, Boukje" uniqKey="De Vries B" first="Boukje" last="De Vries">Boukje De Vries</name><affiliation><nlm:aff id="A3">Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vijfhuizen, Lisanne S" sort="Vijfhuizen, Lisanne S" uniqKey="Vijfhuizen L" first="Lisanne S" last="Vijfhuizen">Lisanne S. Vijfhuizen</name><affiliation><nlm:aff id="A3">Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Anttila, Verneri" sort="Anttila, Verneri" uniqKey="Anttila V" first="Verneri" last="Anttila">Verneri Anttila</name><affiliation><nlm:aff id="A4">Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Winsvold, Bendik S" sort="Winsvold, Bendik S" uniqKey="Winsvold B" first="Bendik S" last="Winsvold">Bendik S. Winsvold</name><affiliation><nlm:aff id="A8">FORMI andDepartment of Neurology, Oslo University Hospital and University of Oslo, Oslo, Norway</nlm:aff></affiliation></author><author><name sortKey="Kurth, Tobias" sort="Kurth, Tobias" uniqKey="Kurth T" first="Tobias" last="Kurth">Tobias Kurth</name><affiliation><nlm:aff id="A9">Institut National de la Santé et de la Recherche Médicale (INSERM) Research Center for Epidemiology and Biostatistics (U897) - Team Neuroepidemiology, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A10">University of Bordeaux, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Department of Medicine, Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Hreinn" sort="Stefansson, Hreinn" uniqKey="Stefansson H" first="Hreinn" last="Stefansson">Hreinn Stefansson</name><affiliation><nlm:aff id="A12">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Kallela, Mikko" sort="Kallela, Mikko" uniqKey="Kallela M" first="Mikko" last="Kallela">Mikko Kallela</name><affiliation><nlm:aff id="A13">Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Malik, Rainer" sort="Malik, Rainer" uniqKey="Malik R" first="Rainer" last="Malik">Rainer Malik</name><affiliation><nlm:aff id="A14">Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Stam, Anine H" sort="Stam, Anine H" uniqKey="Stam A" first="Anine H" last="Stam">Anine H. Stam</name><affiliation><nlm:aff id="A15">Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M Arfan" last="Ikram">M Arfan Ikram</name><affiliation><nlm:aff id="A16">Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Department of Radiology, Erasmus University Medical Centre, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A18">Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ligthart, Lannie" sort="Ligthart, Lannie" uniqKey="Ligthart L" first="Lannie" last="Ligthart">Lannie Ligthart</name><affiliation><nlm:aff id="A19">Department of Biological Psychology, VU University, Amsterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A20">EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Freilinger, Tobias" sort="Freilinger, Tobias" uniqKey="Freilinger T" first="Tobias" last="Freilinger">Tobias Freilinger</name><affiliation><nlm:aff id="A21">Department of Neurology and Epileptology and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Alexander, Michael" sort="Alexander, Michael" uniqKey="Alexander M" first="Michael" last="Alexander">Michael Alexander</name><affiliation><nlm:aff id="A22">Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A23">Institute of Human Genetics, University of Bonn, Bonn, Germany</nlm:aff></affiliation></author><author><name sortKey="Muller Myhsok, Bertram" sort="Muller Myhsok, Bertram" uniqKey="Muller Myhsok B" first="Bertram" last="Muller-Myhsok">Bertram Muller-Myhsok</name><affiliation><nlm:aff id="A24">Max Planck Institute of Psychiatry, Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Munich Cluster for Systems Neurology (SyNergy), Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Schreiber, Stefan" sort="Schreiber, Stefan" uniqKey="Schreiber S" first="Stefan" last="Schreiber">Stefan Schreiber</name><affiliation><nlm:aff id="A26">Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A27">Department of Internal Medicine I, Christian Albrechts University, Kiel, Germany</nlm:aff></affiliation></author><author><name sortKey="Meitinger, Thomas" sort="Meitinger, Thomas" uniqKey="Meitinger T" first="Thomas" last="Meitinger">Thomas Meitinger</name><affiliation><nlm:aff id="A28">Institute of Human Genetics, Helmholtz Center Munich, Neuherberg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Institute of Human Genetics, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Aromaa, Arpo" sort="Aromaa, Arpo" uniqKey="Aromaa A" first="Arpo" last="Aromaa">Arpo Aromaa</name><affiliation><nlm:aff id="A30">National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Eriksson, Johan G" sort="Eriksson, Johan G" uniqKey="Eriksson J" first="Johan G" last="Eriksson">Johan G. Eriksson</name><affiliation><nlm:aff id="A30">National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A31">Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A32">Department of General Practice, Helsinki University Central Hospital, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A33">Vaasa Central Hospital, Vaasa, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Boomsma, Dorret I" sort="Boomsma, Dorret I" uniqKey="Boomsma D" first="Dorret I" last="Boomsma">Dorret I. Boomsma</name><affiliation><nlm:aff id="A19">Department of Biological Psychology, VU University, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M" last="Van Duijn">Cornelia M. Van Duijn</name><affiliation><nlm:aff id="A16">Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zwart, John Anker" sort="Zwart, John Anker" uniqKey="Zwart J" first="John-Anker" last="Zwart">John-Anker Zwart</name><affiliation><nlm:aff id="A8">FORMI andDepartment of Neurology, Oslo University Hospital and University of Oslo, Oslo, Norway</nlm:aff></affiliation></author><author><name sortKey="Quaye, Lydia" sort="Quaye, Lydia" uniqKey="Quaye L" first="Lydia" last="Quaye">Lydia Quaye</name><affiliation><nlm:aff id="A35">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Kubisch, Christian" sort="Kubisch, Christian" uniqKey="Kubisch C" first="Christian" last="Kubisch">Christian Kubisch</name><affiliation><nlm:aff id="A36">Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Dichgans, Martin" sort="Dichgans, Martin" uniqKey="Dichgans M" first="Martin" last="Dichgans">Martin Dichgans</name><affiliation><nlm:aff id="A14">Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Munich Cluster for Systems Neurology (SyNergy), Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Wessman, Maija" sort="Wessman, Maija" uniqKey="Wessman M" first="Maija" last="Wessman">Maija Wessman</name><affiliation><nlm:aff id="A4">Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A31">Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation><nlm:aff id="A12">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A37">School of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Chasman, Daniel I" sort="Chasman, Daniel I" uniqKey="Chasman D" first="Daniel I" last="Chasman">Daniel I. Chasman</name><affiliation><nlm:aff id="A11">Department of Medicine, Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Palotie, Aarno" sort="Palotie, Aarno" uniqKey="Palotie A" first="Aarno" last="Palotie">Aarno Palotie</name><affiliation><nlm:aff id="A4">Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A38">Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A40">Department of Neurology, Massachusetts General Hospital, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G" last="Martin">Nicholas G. Martin</name><affiliation><nlm:aff id="A2">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Montgomery, Grant W" sort="Montgomery, Grant W" uniqKey="Montgomery G" first="Grant W" last="Montgomery">Grant W. Montgomery</name><affiliation><nlm:aff id="A2">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Ferrari, Michel D" sort="Ferrari, Michel D" uniqKey="Ferrari M" first="Michel D" last="Ferrari">Michel D. Ferrari</name><affiliation><nlm:aff id="A15">Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Terwindt, Gisela M" sort="Terwindt, Gisela M" uniqKey="Terwindt G" first="Gisela M" last="Terwindt">Gisela M. Terwindt</name><affiliation><nlm:aff id="A15">Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Den Maagdenberg, Arn M J M" sort="Van Den Maagdenberg, Arn M J M" uniqKey="Van Den Maagdenberg A" first="Arn M J M" last="Van Den Maagdenberg">Arn M J M. Van Den Maagdenberg</name><affiliation><nlm:aff id="A3">Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A15">Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Nyholt, Dale R" sort="Nyholt, Dale R" uniqKey="Nyholt D" first="Dale R" last="Nyholt">Dale R. Nyholt</name><affiliation><nlm:aff id="A1">Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A2">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26660531</idno><idno type="pmc">5541777</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541777</idno><idno type="RBID">PMC:5541777</idno><idno type="doi">10.1177/0333102415591497</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">002014</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002014</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Gene-based pleiotropy across migraine with aura and migraine without aura patient groups</title><author><name sortKey="Zhao, Huiying" sort="Zhao, Huiying" uniqKey="Zhao H" first="Huiying" last="Zhao">Huiying Zhao</name><affiliation><nlm:aff id="A1">Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A2">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Eising, Else" sort="Eising, Else" uniqKey="Eising E" first="Else" last="Eising">Else Eising</name><affiliation><nlm:aff id="A3">Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="De Vries, Boukje" sort="De Vries, Boukje" uniqKey="De Vries B" first="Boukje" last="De Vries">Boukje De Vries</name><affiliation><nlm:aff id="A3">Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vijfhuizen, Lisanne S" sort="Vijfhuizen, Lisanne S" uniqKey="Vijfhuizen L" first="Lisanne S" last="Vijfhuizen">Lisanne S. Vijfhuizen</name><affiliation><nlm:aff id="A3">Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Anttila, Verneri" sort="Anttila, Verneri" uniqKey="Anttila V" first="Verneri" last="Anttila">Verneri Anttila</name><affiliation><nlm:aff id="A4">Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Winsvold, Bendik S" sort="Winsvold, Bendik S" uniqKey="Winsvold B" first="Bendik S" last="Winsvold">Bendik S. Winsvold</name><affiliation><nlm:aff id="A8">FORMI andDepartment of Neurology, Oslo University Hospital and University of Oslo, Oslo, Norway</nlm:aff></affiliation></author><author><name sortKey="Kurth, Tobias" sort="Kurth, Tobias" uniqKey="Kurth T" first="Tobias" last="Kurth">Tobias Kurth</name><affiliation><nlm:aff id="A9">Institut National de la Santé et de la Recherche Médicale (INSERM) Research Center for Epidemiology and Biostatistics (U897) - Team Neuroepidemiology, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A10">University of Bordeaux, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Department of Medicine, Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Hreinn" sort="Stefansson, Hreinn" uniqKey="Stefansson H" first="Hreinn" last="Stefansson">Hreinn Stefansson</name><affiliation><nlm:aff id="A12">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Kallela, Mikko" sort="Kallela, Mikko" uniqKey="Kallela M" first="Mikko" last="Kallela">Mikko Kallela</name><affiliation><nlm:aff id="A13">Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Malik, Rainer" sort="Malik, Rainer" uniqKey="Malik R" first="Rainer" last="Malik">Rainer Malik</name><affiliation><nlm:aff id="A14">Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Stam, Anine H" sort="Stam, Anine H" uniqKey="Stam A" first="Anine H" last="Stam">Anine H. Stam</name><affiliation><nlm:aff id="A15">Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M Arfan" last="Ikram">M Arfan Ikram</name><affiliation><nlm:aff id="A16">Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A17">Department of Radiology, Erasmus University Medical Centre, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A18">Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ligthart, Lannie" sort="Ligthart, Lannie" uniqKey="Ligthart L" first="Lannie" last="Ligthart">Lannie Ligthart</name><affiliation><nlm:aff id="A19">Department of Biological Psychology, VU University, Amsterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A20">EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Freilinger, Tobias" sort="Freilinger, Tobias" uniqKey="Freilinger T" first="Tobias" last="Freilinger">Tobias Freilinger</name><affiliation><nlm:aff id="A21">Department of Neurology and Epileptology and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Alexander, Michael" sort="Alexander, Michael" uniqKey="Alexander M" first="Michael" last="Alexander">Michael Alexander</name><affiliation><nlm:aff id="A22">Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A23">Institute of Human Genetics, University of Bonn, Bonn, Germany</nlm:aff></affiliation></author><author><name sortKey="Muller Myhsok, Bertram" sort="Muller Myhsok, Bertram" uniqKey="Muller Myhsok B" first="Bertram" last="Muller-Myhsok">Bertram Muller-Myhsok</name><affiliation><nlm:aff id="A24">Max Planck Institute of Psychiatry, Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Munich Cluster for Systems Neurology (SyNergy), Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Schreiber, Stefan" sort="Schreiber, Stefan" uniqKey="Schreiber S" first="Stefan" last="Schreiber">Stefan Schreiber</name><affiliation><nlm:aff id="A26">Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A27">Department of Internal Medicine I, Christian Albrechts University, Kiel, Germany</nlm:aff></affiliation></author><author><name sortKey="Meitinger, Thomas" sort="Meitinger, Thomas" uniqKey="Meitinger T" first="Thomas" last="Meitinger">Thomas Meitinger</name><affiliation><nlm:aff id="A28">Institute of Human Genetics, Helmholtz Center Munich, Neuherberg, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Institute of Human Genetics, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Aromaa, Arpo" sort="Aromaa, Arpo" uniqKey="Aromaa A" first="Arpo" last="Aromaa">Arpo Aromaa</name><affiliation><nlm:aff id="A30">National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Eriksson, Johan G" sort="Eriksson, Johan G" uniqKey="Eriksson J" first="Johan G" last="Eriksson">Johan G. Eriksson</name><affiliation><nlm:aff id="A30">National Institute for Health and Welfare, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A31">Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A32">Department of General Practice, Helsinki University Central Hospital, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A33">Vaasa Central Hospital, Vaasa, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A34">Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Boomsma, Dorret I" sort="Boomsma, Dorret I" uniqKey="Boomsma D" first="Dorret I" last="Boomsma">Dorret I. Boomsma</name><affiliation><nlm:aff id="A19">Department of Biological Psychology, VU University, Amsterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M" last="Van Duijn">Cornelia M. Van Duijn</name><affiliation><nlm:aff id="A16">Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zwart, John Anker" sort="Zwart, John Anker" uniqKey="Zwart J" first="John-Anker" last="Zwart">John-Anker Zwart</name><affiliation><nlm:aff id="A8">FORMI andDepartment of Neurology, Oslo University Hospital and University of Oslo, Oslo, Norway</nlm:aff></affiliation></author><author><name sortKey="Quaye, Lydia" sort="Quaye, Lydia" uniqKey="Quaye L" first="Lydia" last="Quaye">Lydia Quaye</name><affiliation><nlm:aff id="A35">Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Kubisch, Christian" sort="Kubisch, Christian" uniqKey="Kubisch C" first="Christian" last="Kubisch">Christian Kubisch</name><affiliation><nlm:aff id="A36">Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Dichgans, Martin" sort="Dichgans, Martin" uniqKey="Dichgans M" first="Martin" last="Dichgans">Martin Dichgans</name><affiliation><nlm:aff id="A14">Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Munich Cluster for Systems Neurology (SyNergy), Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Wessman, Maija" sort="Wessman, Maija" uniqKey="Wessman M" first="Maija" last="Wessman">Maija Wessman</name><affiliation><nlm:aff id="A4">Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A31">Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland</nlm:aff></affiliation></author><author><name sortKey="Stefansson, Kari" sort="Stefansson, Kari" uniqKey="Stefansson K" first="Kari" last="Stefansson">Kari Stefansson</name><affiliation><nlm:aff id="A12">deCODE Genetics, Reykjavik, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A37">School of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Chasman, Daniel I" sort="Chasman, Daniel I" uniqKey="Chasman D" first="Daniel I" last="Chasman">Daniel I. Chasman</name><affiliation><nlm:aff id="A11">Department of Medicine, Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Palotie, Aarno" sort="Palotie, Aarno" uniqKey="Palotie A" first="Aarno" last="Palotie">Aarno Palotie</name><affiliation><nlm:aff id="A4">Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A5">Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A7">Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A38">Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A40">Department of Neurology, Massachusetts General Hospital, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G" last="Martin">Nicholas G. Martin</name><affiliation><nlm:aff id="A2">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Montgomery, Grant W" sort="Montgomery, Grant W" uniqKey="Montgomery G" first="Grant W" last="Montgomery">Grant W. Montgomery</name><affiliation><nlm:aff id="A2">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</nlm:aff></affiliation></author><author><name sortKey="Ferrari, Michel D" sort="Ferrari, Michel D" uniqKey="Ferrari M" first="Michel D" last="Ferrari">Michel D. Ferrari</name><affiliation><nlm:aff id="A15">Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Terwindt, Gisela M" sort="Terwindt, Gisela M" uniqKey="Terwindt G" first="Gisela M" last="Terwindt">Gisela M. Terwindt</name><affiliation><nlm:aff id="A15">Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Van Den Maagdenberg, Arn M J M" sort="Van Den Maagdenberg, Arn M J M" uniqKey="Van Den Maagdenberg A" first="Arn M J M" last="Van Den Maagdenberg">Arn M J M. Van Den Maagdenberg</name><affiliation><nlm:aff id="A3">Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A15">Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Nyholt, Dale R" sort="Nyholt, Dale R" uniqKey="Nyholt D" first="Dale R" last="Nyholt">Dale R. Nyholt</name><affiliation><nlm:aff id="A1">Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A2">QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</nlm:aff></affiliation></author></analytic><series><title level="j">Cephalalgia : an international journal of headache</title><idno type="ISSN">0333-1024</idno><idno type="eISSN">1468-2982</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Introduction</title><p id="P3">It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related.</p></sec><sec id="S2"><title>Aim</title><p id="P4">Using a novel gene-based (statistical) approach we aimed to identify individual genes and pathways associated with both MA and MO.</p></sec><sec id="S3"><title>Methods</title><p id="P5">Gene-based tests were performed utilizing genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4,505 MA cases with 34,813 controls and 4,038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO.</p></sec><sec id="S4"><title>Results</title><p id="P6">We found a significant overlap in genes associated with MA and MO. Of the total 1,514 genes with a nominally significant gene-based <italic>P</italic>-value (<italic>P</italic><sub>gene-based</sub> ≤ 0.05) in the MA subgroup, 107 also produced <italic>P</italic><sub>gene-based</sub> ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (<italic>P</italic><sub>binomial-test</sub> = 1.6×10<sup>−3</sup>). Combining results across MA and MO, six genes produced genome-wide significant gene-based <italic>P</italic>-values. Four of these genes (<italic>TRPM8, UFL1</italic>, <italic>FHL5</italic> and <italic>LRP1</italic>) were located in close proximity to previously reported genome-wide significant SNPs for migraine; while two genes, <italic>TARBP2</italic> and <italic>NPFF</italic> separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue.</p></sec><sec id="S5"><title>Conclusions</title><p id="P7">Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (<italic>NPFF</italic>) as a novel candidate risk gene for both types of migraine.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8200710</journal-id><journal-id journal-id-type="pubmed-jr-id">2844</journal-id><journal-id journal-id-type="nlm-ta">Cephalalgia</journal-id><journal-id journal-id-type="iso-abbrev">Cephalalgia</journal-id><journal-title-group><journal-title>Cephalalgia : an international journal of headache</journal-title></journal-title-group><issn pub-type="ppub">0333-1024</issn><issn pub-type="epub">1468-2982</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26660531</article-id><article-id pub-id-type="pmc">5541777</article-id><article-id pub-id-type="doi">10.1177/0333102415591497</article-id><article-id pub-id-type="manuscript">NIHMS887292</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Gene-based pleiotropy across migraine with aura and migraine without aura patient groups</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Huiying</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="author-notes" rid="FN2">#</xref></contrib><contrib contrib-type="author"><name><surname>Eising</surname><given-names>Else</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="author-notes" rid="FN2">#</xref></contrib><contrib contrib-type="author"><name><surname>de Vries</surname><given-names>Boukje</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Vijfhuizen</surname><given-names>Lisanne S</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><collab>for the International Headache Genetics Consortium</collab></contrib><contrib contrib-type="author"><name><surname>Anttila</surname><given-names>Verneri</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Winsvold</surname><given-names>Bendik S</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Kurth</surname><given-names>Tobias</given-names></name><xref ref-type="aff" rid="A9">9</xref><xref ref-type="aff" rid="A10">10</xref><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Stefansson</surname><given-names>Hreinn</given-names></name><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Kallela</surname><given-names>Mikko</given-names></name><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Malik</surname><given-names>Rainer</given-names></name><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Stam</surname><given-names>Anine H</given-names></name><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Ikram</surname><given-names>M Arfan</given-names></name><xref ref-type="aff" rid="A16">16</xref><xref ref-type="aff" rid="A17">17</xref><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>Ligthart</surname><given-names>Lannie</given-names></name><xref ref-type="aff" rid="A19">19</xref><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Freilinger</surname><given-names>Tobias</given-names></name><xref ref-type="aff" rid="A21">21</xref><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Alexander</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="A22">22</xref><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Muller-Myhsok</surname><given-names>Bertram</given-names></name><xref ref-type="aff" rid="A24">24</xref><xref ref-type="aff" rid="A25">25</xref></contrib><contrib contrib-type="author"><name><surname>Schreiber</surname><given-names>Stefan</given-names></name><xref ref-type="aff" rid="A26">26</xref><xref ref-type="aff" rid="A27">27</xref></contrib><contrib contrib-type="author"><name><surname>Meitinger</surname><given-names>Thomas</given-names></name><xref ref-type="aff" rid="A28">28</xref><xref ref-type="aff" rid="A29">29</xref></contrib><contrib contrib-type="author"><name><surname>Aromaa</surname><given-names>Arpo</given-names></name><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>Eriksson</surname><given-names>Johan G</given-names></name><xref ref-type="aff" rid="A30">30</xref><xref ref-type="aff" rid="A31">31</xref><xref ref-type="aff" rid="A32">32</xref><xref ref-type="aff" rid="A33">33</xref><xref ref-type="aff" rid="A34">34</xref></contrib><contrib contrib-type="author"><name><surname>Boomsma</surname><given-names>Dorret I</given-names></name><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>van Duijn</surname><given-names>Cornelia M</given-names></name><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Zwart</surname><given-names>John-Anker</given-names></name><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Quaye</surname><given-names>Lydia</given-names></name><xref ref-type="aff" rid="A35">35</xref></contrib><contrib contrib-type="author"><name><surname>Kubisch</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="A36">36</xref></contrib><contrib contrib-type="author"><name><surname>Dichgans</surname><given-names>Martin</given-names></name><xref ref-type="aff" rid="A14">14</xref><xref ref-type="aff" rid="A25">25</xref></contrib><contrib contrib-type="author"><name><surname>Wessman</surname><given-names>Maija</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A31">31</xref></contrib><contrib contrib-type="author"><name><surname>Stefansson</surname><given-names>Kari</given-names></name><xref ref-type="aff" rid="A12">12</xref><xref ref-type="aff" rid="A37">37</xref></contrib><contrib contrib-type="author"><name><surname>Chasman</surname><given-names>Daniel I</given-names></name><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Palotie</surname><given-names>Aarno</given-names></name><xref ref-type="aff" rid="A4">4</xref><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A38">38</xref><xref ref-type="aff" rid="A39">39</xref><xref ref-type="aff" rid="A40">40</xref></contrib><contrib contrib-type="author"><name><surname>Martin</surname><given-names>Nicholas G</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Montgomery</surname><given-names>Grant W</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Ferrari</surname><given-names>Michel D</given-names></name><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Terwindt</surname><given-names>Gisela M</given-names></name><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>van den Maagdenberg</surname><given-names>Arn M J M</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref ref-type="aff" rid="A15">15</xref><xref ref-type="author-notes" rid="FN3">*</xref></contrib><contrib contrib-type="author"><name><surname>Nyholt</surname><given-names>Dale R</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref><xref ref-type="author-notes" rid="FN3">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia</aff><aff id="A2"><label>2</label>QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia</aff><aff id="A3"><label>3</label>Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands</aff><aff id="A4"><label>4</label>Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA</aff><aff id="A5"><label>5</label>Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA</aff><aff id="A6"><label>6</label>Harvard Medical School, Boston, MA, USA</aff><aff id="A7"><label>7</label>Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA</aff><aff id="A8"><label>8</label>FORMI andDepartment of Neurology, Oslo University Hospital and University of Oslo, Oslo, Norway</aff><aff id="A9"><label>9</label>Institut National de la Santé et de la Recherche Médicale (INSERM) Research Center for Epidemiology and Biostatistics (U897) - Team Neuroepidemiology, Bordeaux, France</aff><aff id="A10"><label>10</label>University of Bordeaux, Bordeaux, France</aff><aff id="A11"><label>11</label>Department of Medicine, Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA</aff><aff id="A12"><label>12</label>deCODE Genetics, Reykjavik, Iceland</aff><aff id="A13"><label>13</label>Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland</aff><aff id="A14"><label>14</label>Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany</aff><aff id="A15"><label>15</label>Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands</aff><aff id="A16"><label>16</label>Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands</aff><aff id="A17"><label>17</label>Department of Radiology, Erasmus University Medical Centre, Rotterdam, The Netherlands</aff><aff id="A18"><label>18</label>Department of Neurology, Erasmus University Medical Centre, Rotterdam, The Netherlands</aff><aff id="A19"><label>19</label>Department of Biological Psychology, VU University, Amsterdam, The Netherlands</aff><aff id="A20"><label>20</label>EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands</aff><aff id="A21"><label>21</label>Department of Neurology and Epileptology and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Germany</aff><aff id="A22"><label>22</label>Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany</aff><aff id="A23"><label>23</label>Institute of Human Genetics, University of Bonn, Bonn, Germany</aff><aff id="A24"><label>24</label>Max Planck Institute of Psychiatry, Munich, Germany</aff><aff id="A25"><label>25</label>Munich Cluster for Systems Neurology (SyNergy), Munich, Germany</aff><aff id="A26"><label>26</label>Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel, Germany</aff><aff id="A27"><label>27</label>Department of Internal Medicine I, Christian Albrechts University, Kiel, Germany</aff><aff id="A28"><label>28</label>Institute of Human Genetics, Helmholtz Center Munich, Neuherberg, Germany</aff><aff id="A29"><label>29</label>Institute of Human Genetics, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany</aff><aff id="A30"><label>30</label>National Institute for Health and Welfare, Helsinki, Finland</aff><aff id="A31"><label>31</label>Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland</aff><aff id="A32"><label>32</label>Department of General Practice, Helsinki University Central Hospital, Helsinki, Finland</aff><aff id="A33"><label>33</label>Vaasa Central Hospital, Vaasa, Finland</aff><aff id="A34"><label>34</label>Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland</aff><aff id="A35"><label>35</label>Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK</aff><aff id="A36"><label>36</label>Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany</aff><aff id="A37"><label>37</label>School of Medicine, University of Iceland, Reykjavik, Iceland</aff><aff id="A38"><label>38</label>Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland</aff><aff id="A39"><label>39</label>Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA</aff><aff id="A40"><label>40</label>Department of Neurology, Massachusetts General Hospital, Boston, MA, USA</aff><author-notes><corresp id="FN1"><bold>Corresponding author:</bold> Dale R Nyholt, Institute of Health and Biomedical Innovation, Queensland University of Technology, GPO Box 2434, Brisbane QLD 4001, Australia. Telephone: +61 7 31386000. <email>d.nyholt@qut.edu.au</email></corresp><fn id="FN2" fn-type="equal"><label>#</label><p id="P1">These authors contributed equally to this work.</p></fn><fn id="FN3"><label>*</label><p id="P2">These authors jointly directed this work.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>27</day><month>6</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>08</day><month>12</month><year>2015</year></pub-date><pub-date pub-type="ppub"><month>6</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>03</day><month>8</month><year>2017</year></pub-date><volume>36</volume><issue>7</issue><fpage>648</fpage><lpage>657</lpage><pmc-comment>elocation-id from pubmed: 10.1177/0333102415591497</pmc-comment>
<abstract><sec id="S1"><title>Introduction</title><p id="P3">It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related.</p></sec><sec id="S2"><title>Aim</title><p id="P4">Using a novel gene-based (statistical) approach we aimed to identify individual genes and pathways associated with both MA and MO.</p></sec><sec id="S3"><title>Methods</title><p id="P5">Gene-based tests were performed utilizing genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4,505 MA cases with 34,813 controls and 4,038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO.</p></sec><sec id="S4"><title>Results</title><p id="P6">We found a significant overlap in genes associated with MA and MO. Of the total 1,514 genes with a nominally significant gene-based <italic>P</italic>-value (<italic>P</italic><sub>gene-based</sub> ≤ 0.05) in the MA subgroup, 107 also produced <italic>P</italic><sub>gene-based</sub> ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (<italic>P</italic><sub>binomial-test</sub> = 1.6×10<sup>−3</sup>). Combining results across MA and MO, six genes produced genome-wide significant gene-based <italic>P</italic>-values. Four of these genes (<italic>TRPM8, UFL1</italic>, <italic>FHL5</italic> and <italic>LRP1</italic>) were located in close proximity to previously reported genome-wide significant SNPs for migraine; while two genes, <italic>TARBP2</italic> and <italic>NPFF</italic> separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue.</p></sec><sec id="S5"><title>Conclusions</title><p id="P7">Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (<italic>NPFF</italic>) as a novel candidate risk gene for both types of migraine.</p></sec></abstract><kwd-group><kwd>Migraine</kwd><kwd>aura</kwd><kwd>genome-wide</kwd><kwd>association</kwd><kwd>gene-based</kwd><kwd>pleiotropy</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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